Many of the hereditary diseases are related to defects in genes that would otherwise be expressed in hepatocytes. Examples of these diseases including alpha-1-antitrypsin deficiency and hemophilia. The development of an efficient gene therapy vector to target genes into hepatocytes of patients with these types of hereditary diseases can potentially improve the quality of lives of these patients. Hepatitis B virus (HBV) is a DNA virus with a high liver-specificity. A gene-therapy vector based on this virus will likely be an effective vector for targeting genes to hepatocytes. Furthermore, unlike current gene-therapy protocols which often involve complicated surgical procedures, patients can be treated with simple i.v. injections of the recombinant HBV virus carrying the desired gene. The goal of this project is to develop an HBV-based vector for liver-targeted gene therapy.